The overall goal of this K01 proposal is to support Jennifer Han, M.D., M.S.C.E., to become an independent investigator in the field of healthcare-associated infections and antimicrobia-resistant organisms, with a specific focus on the post-acute care setting. Antimicrobial resistance is a critical public health problem and is associated with significant morbidity, mortality, and healthcare costs. Post-acute care settings, and long-term acute care hospitals (LTACHs) in particular, are increasingly important sites of clinical care in the United States. Given high rates of antimicrobial and medical device use, prolonged lengths of stay, and complex patient populations with acute medical needs, patients in LTACHs are at significant risk for infection with antimicrobial-resistant organisms. However, despite th dramatic and continued rise in the LTACH population in recent years, there are very few data on the epidemiology of antimicrobial-resistant organisms in this healthcare setting. In this proposal, the candidate will elucidate the epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) in the LTACH setting. The prevalence of CRKP in the past decade has increased at an alarming rate such that CRKP is now endemic in many parts of the world, including areas of the United States. Given the lack of effective antimicrobal treatment options, as well as high associated mortality rates, CRKP represent perhaps the most significant challenge in antimicrobial-resistant organisms. This proposal adopts an interdisciplinary approach, and will link the clinical and molecular epidemiology of CRKP to substantially improve the understanding of CRKP infections in the LTACH setting. The specific aims of this proposal are: Aim 1: to provide comprehensive genotypic and phenotypic characterization of CRKP isolates (including resistance mechanisms) from a large, nationally-widespread network of LTACHs. Aim 2: to elucidate risk factors for infectio with CRKP in the LTACH setting. Aim 3: to evaluate the clinical impact of CRKP infection in the LTACH setting. The hypotheses for these aims are: 1) the phenotypic and genotypic characteristics of CRKP isolates will be rigorously identified~ 2) prior carbapenem use is associated with CRKP infection~ and 3) CRKP infections are associated with increased mortality. The results of the proposed research will significantly infom future intervention studies with the goal of decreasing infection-associated morbidity an mortality in LTACHs. This proposal represents a five-year comprehensive mentoring, research, and didactic plan to transition the candidate to a successful independent investigator in antimicrobial resistance. At the conclusion of the award period, the candidate will have contributed substantially to knowledge of the epidemiology of CRKP infection in a healthcare setting of increasing importance. In addition, the candidate will be poised o become a leader in conducting clinical epidemiologic research to limit the emergence of antimicrobial-resistant organisms in post-acute care settings as well as improve associated clinical outcomes.